The Alpha-Tocopherol, Beta-Carotene Lung Cancer Prevention Study (ATBC Study) is investigating the efficacy of daily oral alpha-tocopherol (50 mg) and beta-carotene (20 mg) in a double-blind, randomized 2x2 factorial design trial aimed at preventing lung cancer among 50-69 year old male cigarette smokers. The project is based on experimental and epidemiological research which demonstrates a potential preventive role for these agents. Recruitment took place between 1985-88, and the trial intervention ended on schedule March 31, 1993 after an average followup of over 6 years. A postal survey screening for potential trial participants was sent to 291,000 men in southern Finland, and 76% responded. We invited the smokers willing to participate (43,000) to one of 13 study clinics, and over 29,000 were randomized into the study. Compliance to the one capsule daily regimen has remained very high (97% average), and the dropout rate averages less than 6% per year. Reduction of lung cancer incidence in the active agent groups is the primary study goal; differences in the occurrence of other cancers will also be evaluated. Several pilot studies in support of the trial have also been completed including a feasibility study, validation of study dietary questionnaires, and evaluation of skin yellowing and serum levels following beta-carotene administration. This trial is being conducted collaboratively with the Surveillance Program and the Biometry Branch of the Division of Cancer Prevention and Control and with the National Public Health Institute of Finland.